TRANSEPITHELIAL SIGNALING TO NEUTROPHILS BY SALMONELLAE - A NOVEL VIRULENCE MECHANISM FOR GASTROENTERITIS

Salmonella serotypes which elicit human enteritis cannot he distinguis hed from those that do not on the basis of their in vitro Interactions with eukaryotic cells. We have recently reported that an enteritis-pr oducing strain of Salmonella typhimurium signals intact intestinal epi thelium to recruit subepithelial neutrophils to migrate across the epi thelia (B. A. McCormick, S. P. Colgan, C. D. Archer, S. I. Miller, and J. L. Madara, J. Cell Biol. 123:895-907, 1993). We now utilize a cell culture model of human intestinal epithelium (with T84 cells) to exam ine whether such transepithelial signaling to neutrophils by salmonell ae is predictive of potential to elicit gastroenteritis. Various Salmo nella serotypes, including S. typhimurium, S. enteritidis, S. pullorum S. arizonae, S. typhi, and S. paratyphi, as well as invasion-defectiv e mutants of S. typhimurium, were studied. Strains or serotypes which elicit diffuse enteritis in humans (defined histologically as transepi thelial migration of neutrophils) exhibited transepithelial signaling to neutrophils across epithelial cell monolayers, while those which do not elicit diffuse enteritis in humans did not display transepithelia l signaling. In contrast, the ability to enter the apical surface of T 84 cells did not differentiate strains or serotypes which induce diffu se enteritis from those which do not. These results strongly suggest t hat the ability of salmonellae to elicit transepithelial signaling to neutrophils is a key virulence mechanism underlying Salmonella-elicite d enteritis.